Bioactive Hydrogel Platforms for Spatiotemporal Delivery of Baculoviruses in Biomedical Applications

Baculoviruses offer a multitude of advantages over other gene carriers due to their non-pathogenicity and inability to replicate in mammalian cells, ease of production, and high transduction efficiencies. To expand their functionality in vivo, baculoviruses containing mammalian transcription promoters (BacMam) can be physically entrapped within biocompatible hydrogels to modulate their release and transduction efficiency. The present work demonstrates several techniques in which BacMam viruses can be encapsulated and delivered in fibrin gel, an FDA-approved sealant and adhesive with numerous clinical applications, to provide spatiotemporal control over the delivery of BacMam viruses to mammalian cells. Fibrin is shown to be an effective biomaterial carrier for the delivery of BacMam viruses to mammalian cells growing in 2D culture, 3D culture, and in the co-delivery of stem cells and baculoviruses in the aerosolized delivery of fibrin films. Overall, the results of this work provide a valuable insight on the therapeutic potential of fibrin gels for in vivo BacMam-mediated gene delivery in regenerative medicine.